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Pediatric Endocrinology Reviews (PER) is the most respected international peer reviewed journal in Pediatric Diabetes, Nutrition Metabolism and Genetics. Hypothyriodism, Hyperthyriodism, Glycemic Management for Children with Diabetes Glucose Monitoring Adrenal Insufficiency Turner Syndrome Late Adolescence Klinefelter Syndrome Children with Short Stature and Growth Failure: Heightism Type 1 Diabetes in Children Growth Hormone Treatment for GHD Insulin-like Growth Factor-I Growth Hormone Deficiency SGA Children with Short Stature Receiving GH Treatment Hypothalamic Obesity Adolescent Gynecomastia Hematospermia in Adolescents Gain-of-Function CDKN1C Mutations Craniopharyngioma Succinate-Dehydrogenase Deficient Paragangliomas/Pheochromocytomas Adrenal Steroidogenesis: Impact on Gonadal Function Focal Congenital Hyperinsulinism (CHI)  Longevity Hormone Klotho Pediatric Congenital Hypothyroid Lysosomal Storage Diseases Juvenile NCL (CLN3 Disease) GM1 and GM2 Gangliosidoses Types A and B Niemann-Pick Disease CLN2 Disease (Classic Late Infantile Neuronal Ceroid Lipofuscinosis) Krabbe Disease Fucosidosis Nuclear Factor Kappa B (NF-κB) in Growth Plate Chondrogenesis Persistent Müllerian Duct Syndrome LHX4 Gene Alterations Stunted Growth 45,X/46,XY Gonadal Dysgenesis Thyroid Hemiagenesis Nutrimetabolomics and Adipocitokines Chromosomal Microarray Analysis (CMA) Chromosomal microarray, Copy Number Variant (CNV), Prenatal, Amniocentesis, Comparative genomic hybridization, SNP array, Diagnosis, Clinical Abreviations: aCGH – array-based comparative genomic hybridization, ASD – autism spectrum disorder, BAC – bacterial artificial chromosome, CHD – congenital heart disease, CMA – chromosomal microarray analysis, CNV – copy number variant, CVS – chorionic villus sampling, DD – developmental delay, DNA – deoxyribonucleic acid, FISH – fluorescent in situ hybridization, GABA - gammaaminobutyric acid, ID – intellectual disability, LOH – loss of heterozygosity, NGS – next generation sequencing, NIPT – noninvasive prenatal testing, NOS – not otherwise specified, PGD - preimplantation genetic diagnosis, SNP – single nucleotide polymorphism, VUS – variant of unclear clinical significance Central precocious puberty, Traumatic brain injury, Pathophysiology Nephrolithiasis, Nephrocalcinosis, Hypercalciuria, Hyperoxaluria, Hypouricemia, Cystinuria, Genetics 

Vol. 8 supplement 2

March 2011

 

Disturbances of Biomarkers of Iron and Oxidant-Antioxidant Homeostasis in Patients with beta-Thalassemia Intermedia

Christos Kattamis1, MD, Christina Lazaropoulou2, BSc, Polyxeni Delaporta1, MD, Filia Apostolakou2, MSc, Antonios Kattamis1, MD and Ioannis Papassotiriou2, PhD

Abstract

Background: Disturbances of oxidative stress and antioxidant status have been reported in patients with β-ThM and in a limited number of patients with ThI. Objectives: To I) study relevant biomarkers of iron metabolism, oxidative stress and antioxidant status, in untransfused patients with ThI and II) evaluate the relation of changes in biomarkers to the clinicalhematological phenotype and genotype. Design: Biomarkers of iron metabolism (ferritin, NTBI, sTfR), of oxidant activity (MDA, GSSG, GSSC/GSHT, NO) and of antioxidant enzymes (GR, GPx, SOD) and Vitamins (E, C, A) were estimated and analyzed in 20 controls and 33 patients with ThI, sub-classified into mild (17) and severe (16) types. All but five were untransfused. Results: Clinical phenotypes of mild and severe ThI were related to distinct genotypes, 11 for mild and 14 for severe. The three iron biomarkers were significantly increased in both ThI types compared to controls and in severe compared to mild types. The ferritin levels (total iron load) had a highly significant positive correlation with age (p<0.001) and sTfR. Biomarkers with oxidant activity were also significantly increased in ThI patients compared to controls; significantly higher levels for MDA, NTBI, and GSSG/GSHT were found in severe ThI. The activity of antioxidant enzymes GR, GP and SOD, was significantly significantly reduced in patients, especially in the severe type. Vitamin C was mildly reduced in both types of ThI. Conclusions: Activity of relevant biomarkers of iron and oxidant-antioxidant homeostasis was significantly increased in untransfused patients with ThI. These changes coincide with the severity of clinical phenotype, genotype and bone marrow erythroid activity evaluated by sTfR levels.

Ref: Ped. Endocrinol. Rev. 2011;8(Suppl 2):256-262

Key words: Thalassemia intermedia, biomarkers, bone marrow activity, oxidative stress, iron metabolism, red cell antioxidant enzymes, antioxidant vitamins

Abbreviations: ThM, Thalassemia major; ThI, Thalassemia Intermedia; NTBI, non transferrin bound iron; GR, glutathione reductase; GPx glutathione peroxidase; GSSG, oxidized glutathione; GSH, reduced glutathione; MDA, malonyldialdehyde; SOD, superoxide dismutase; NO, nitric oxide; BMA, bone marrow erythroid activity

 

 

Pathophysiology of Beta Thalassaemia

Raffaella Origa1, MD, Renzo Galanello2, MD

Abstract

In beta thalassemia, unbalanced alpha globin chain synthesis results in severely rheologically compromised erythrocytes with premature destruction in the peripheral circulation and ineffective erythropoiesis within the bone marrow and in extramedullary sites. In nontransfused beta thalassemia patients, erythropoiesis, anemia and hypoxia down-regulate hepcidin, the master regulator of iron homeostasis. Hepcidin deficiency in turn allows excessive duodenal iron absorption and development of systemic iron overload. In regularly transfused patients iron overload is mostly due to red cell breakdown. When the iron binding capacity of transferrin is saturated, iron can appear in the serum in a free form, called Non-Transferrin-Bound Iron, a powerful catalyst for the formation of free radicals, capable of causing oxidative stress and damage to mitochondria, lysosomes, lipid membranes, proteins, and DNA. Apart from the iron overload-related complications, other pathological conditions such as bone disease, gallstones and thromboembolic events occur in a relevant proportion of subjects with thalassemia.

Ref: Ped. Endocrinol. 2011;8(suppl. 2):263-270

Key words: Thalassemia major, thalassemia intermedia, pathophysiology, ineffective erythropoiesis, hepcidin, osteoporosis, gallstones, thrombosis

 

 

The Multifactorial Origin of Growth Failure in Thalassaemia

Nicos Skordis1, MD, Andreas Kyriakou2, MD

Abstract

Growth failure in thalassaemia major (TM) has been recognised for many years, and has persisted despite major therapeutic advances. The child with TM has a particular growth pattern, which is relatively normal until age 9-10 years; after this age a slowing down of growth velocity and reduced or absent pubertal growth spurt are observed. The pathogenesis of growth failure is multifactorial. The fundamental problem is the free iron and hemosiderosis-induced damage of the endocrine glands. Additional factors may contribute to the aetiology of growth delay including chronic anaemia and hypoxia, chronic liver disease, zinc and folic acid and nutritional deficiencies, intensive use of chelating agents, emotional factors, endocrinopathies (hypogonadism, delayed puberty, hypothyroidism, disturbed calcium homeostasis and bone disease) and last but not least dysregulation of the GH-IGF-1 axis. Three phases of growth disturbances according to age of presentation are well recognised, and have different aetiologies: in the first phase growth disturbance is mainly due to hypoxia, anaemia, ineffective erythropoiesis and nutritional factors. During late childhood (second phase), growth retardation is mainly due to iron overload affecting GH-IGF-1 axis and other potential endocrine complications. Although appropriate iron chelation therapy can improve growth and development, TM children and adolescents treated intensively with desferrioxamine remain short as well, showing body disproportion between the upper and lower body segment. After the age of 10-11 years (third phase), delayed or arrested puberty is an important contributing factor to growth failure in adolescent thalassaemics, who do not exhibit a normal growth spurt. During the last decades therapeutic progress and bone marrow transplantation resulted in a prolonged life expectancy in TM patients. Growth retardation, however, continues to be a significant challenge in these individuals, often affecting their social adjustment and quality of life.

Ref: Ped. Endocrinol. Rev. 2011;8(Suppl 2):271-277

Keywords: Thalassaemia, growth failure, endocrine complications

 

 

Age Related IGF-I Changes and IGF-I Generation in Thalassemia Major

Ashraf T. Soliman1,MD, PhD, FRCP, Ahmed Abushahin2,MD, Khalid Abohezeima3,MD, Hany Khalafallah4,MD, Ashraf Adel5,MD, Ahmed Elawwa6,MD, Naima Elmulla7 MD

Abstract

We measured serum concentrations of insulin like growth factor-I (IGF-I) in 20 thalassemic males with short stature (height SDS <-2) and/or slow growth velocity (GV <-1 SD) throughout their childhood and adolescence, compared these data with normal reference data validated in our lab, and evaluated their growth hormone secretion in response to clonidine and glucagon stimulation. We also performed IGF-I generation test on 26 patients with beta thalassemia major (BTM) before and after blood transfusion to evaluate the effect of increased hemoglobin (Hb) on IGF-I and its response to GH. We obtained the following results. 1) No statistical difference in age, HSDS, target height SDS or bone age was observed between BTM patients with growth hormone deficiency (GHD) compared to those with normal GH secretion (GHS). 2) The age-related levels in serum total IGF-I in thalassemic males were significantly decreased from early childhood to 18 years of age compared to normal subjects. Thalassemic males with GHD did not show any significant peak of IGF-I levels until 18 years of age, whereas thalassemic males with normal GH response to provocation (GHS) achieved a significant peak level of IGF-I that was attenuated and late compared to normal males. The basal serum IGF-I concentrations at different ages did not differ between the GHD and GHS groups until the age of 12 years. After 12 years of age, IGF-I levels were significantly higher in thalassemic children with GHS. A significant increase in the circulating basal IGF-I concentrations from 53 +/-35 ug/l to 82.6 +/- 39 ug/L was achieved with increasing Hb concentration after blood transfusion. The serum total IGF-I levels increased significantly with the administration of human growth hormone (hGH) for 4 days, both before and after blood transfusion. The peak IGF-I response to GH injections did not differ before compared to after blood transfusion. The percent increment of IGF-I levels generated after GH injections was higher in thalassemic children with GHD as compared to those with GHS both before and after blood transfusion. In conclusion, our results showed that agerelated serum IGF-I concentrations were significantly lower in short thalassemic patients, with and without GHD, during childhood and adolescence, compared to normal standards. Correction of anemia significantly increased serum concentration of IGF-I but does not affect the increase of IGF-I in response to GH stimulation.

Ref: Ped. Endocrinol. Rev. 2011;8(Suppl 2):278-283

Key words: Beta-thalassaemia major, short stature, hemoglobin, growth hormone, IGF-I generation

 

 

GH Deficiency in Adult Β-Thalassemia Major Patients and Its Relationship with IGF-1 Production

Angela Ida Pincelli1, MD, Nicoletta Masera2, MD, Luisa Tavecchia3, MD, Mario Perotti1, MD, Silvia Perra1, MD, Raffaela Mariani1, MD, Alberto Piperno1, MD, Giuseppe Mancia1, MD, Guido Grassi1, MD, Giuseppe Masera2, MD

Abstract

Endocrine complications in β-thalassemia represent a prominent cause of morbidity. Above all, dysfunction of GH-IGF-1 axis is of a major concern because of its pathogenic role on cardiac and bone disease, frequently described in this clinical setting. The aim of this paper is to analyze GH-IGF-1 axis in a cohort of 25 adult patients affected by β-thalassemia. We found that GH deficiency was present in only 8% of our patients if diagnosis was based on GH peak below 9μg/L to two GH provocative tests instead of only one, and was mainly related to iron overload. On the contrary, IGF-1 production was impaired in a higher percentage of patients (72%), without significant correlation with iron burden. Of note, patients with hepatitis C virus infection showed lower IGF-1 concentrations than uninfected subjects despite a normal GH reserve, suggesting that partial GH insensitivity at the post-receptor level may play a key role in IGF-1 deficiency described in thalassemic patients

Ref: Ped. Endocrinol. Rev. 2011;8(Suppl. 2):284-289

Key words: Thalassemia major, GH deficiency, GH provocative tests, IGF-1 synthesis, HCV infection, osteoporosis

 

 

Growth Hormone and Adrenal Response to Intramuscular Glucagon Test and Its Relationship to IGF-1 Production and Left Ventricular Ejection Fraction in Adult Β-Thalassemia Major Patients

Vincenzo De Sanctis1, MD, Nicos Skordis2, MD, Maria Concetta Galati3, MD, Giuseppe Raiola4, MD, Michela Giovannini5, MD, Giancarlo Candini6, PhD, Katerina Kaffe2, MD, Irene Savvides7, MD, Soteroulla Christou7, MD

Abstract

In patients with b-thalassemia major (TM), the anterior pituitary gland is particularly sensitive to free radical stresses. It has been reported that the GH deficiency (GHD) may be secondary to either pituitary or hypothalamic dysfunction. The duration of the disease, the patient’s age and the severity of iron overload are the most important factors responsible for the defect of growth hormone (GH) secretion. Recent reports have documented a frequency of severe growth hormone deficiency in 13%-32% of patients with b-thalassemia major. All of these patients underwent GH-releasing hormone (GH-RH) plus arginine (ARG) testing. We undertook the present study to evaluate the GH and adrenal response during glucagon stimulation test (GST) in patients with TM because the GH-RH plus ARG test in patients with hypothalamic GHD may be misleading. Thirty-three adult TM patients were recruited (mean age 36.6 years). Fifty four percent were included in the severe GHD group (GH peak below 3mg/l). The IGF-1 level in TM patients was consistently low (60.3±35.3 mg/l) and 86.6% of patients with a normal GH response to GST had a low IGF-1 level. These findings are also indicative of a relative resistance to GH. In eight out of 18 TM patients (44.4%), the GHD was associated with hypogonadotropic hypogonadism. A positive correlation was found between GH peak after GST and IGF-1 level (r = 0.8, p: 0.003) and a negative correlation between the age of female TM patients and GH peak (r = 0.711, p: 0.007). All patients but one had no evidence of cardiac iron overload (mean T2* 30.4±8.2 ms; range 14-44 ms). The mean LVEF (%) in TM patients was no different when compared to healthy controls. However, three patients with severe GHD and normal T2*were found to have reduced LVEF. One patient (4%) had a peak cortisol response to GST compatible to adrenal insufficiency. Nausea, headache and\or hypoglycemia occurred in 3 patients (12%) during GST. In conclusion, our study demonstrates that the presence of GHD is frequent in adult TM patients. According to the international guidelines for medical practice, we believe that before considering hormone replacement therapy, a second test to confirm the diagnosis of GHD and adrenal insufficiency is required.

Ref: Ped. Endocrinol Rev. 2011;8(Suppl 2):290-294

Key words: Thalassemia, growth hormone deficiency, IGF-1, adrenal, heart, adults.

 

 

Adrenal Function in Thalassemia Major Adolescents

Heba H. Elsedfy1, MD, M. El Kholy1, MD, R. Tarif1, MD, AI Hamed2 MD M. Elalfy1, MD

Abstract

Background: Several studies reported a significant prevalence of adrenal insufficiency, ranging from 18-45%, in patients with thalassemia. Evidence for dissociation of cortisol and adrenal androgen secretion in patients with beta-thalassemia was previously reported. Aim: We measured adrenal androgen response along with cortisol to the standard (250 mg) dose ACTH test. Methods: Forty five beta-thalassemia major (TM) patients were enrolled. Their ages ranged between 12 and 20 years (14.9± 2.2 years). All patients underwent the 250 mg cosyntropin test in the morning before blood transfusion. Blood samples for total cortisol, dehdroepiandrosterone (DHEA) and androstendione (A) measurements were collected before and 60 min after IV injection of 250 mg cosyntropin. Adrenal insufficiency was observed in 7 of 45 (15.5%) patients. Adrenal androgen levels decreased significantly with advancing Tanner stage. No difference was noted between patients with and without adrenal insufficiency regarding anthropometric and laboratory parameters.

Conclusion: Adrenal insufficiency is not a rare complication in thalassemia. Adrenal androgen production declines with advancing puberty in thalassemic adolescents and might explain the poor development of pubic and axillary hair observed in this condition.

Ref: Ped. Endocrinol. Rev. 2011;8(Suppl. 2):295-299

Key words: thalassaemia, adrenal function, adolescents

 

 

Bone Disease in Thalassaemia Major: Recent Advances in Pathogenesis and Clinical Aspects

Nicos Skordis1, MD, Meropi Toumba1, MD

Abstract

Bone is a dynamic organ, constantly changing metabolically and being remodelled through the balanced activity of osteoclast and osteoblast on trabecular surfaces. Osteoporosis represents a continuum, in which multiple pathogenic mechanisms converge to cause loss of bone mass and deterioration of microarchitecture of skeletal structure. In thalassaemia major (TM), progressive ‘aging’ of bone starts in early childhood, through the gradual development of an imbalance between augmented osteoclastic resorption and insufficient osteoblastic bone formation. Chronic anemia, iron toxicity and endocrine complications, via a complex mechanism, lead to alterations in the RANK/RANKL/OPG system in favor of increased osteoclastic activity and enhanced osteoblastic dysfunction. Hypogonadotrophic hypogonadism and delayed puberty are the most common endocrine complications in patients with TM; they also contribute to osteopenia and osteoporosis, which is present in more than 50% of patients. There are gender differences not only in the prevalence but also in the severity of the osteoporosis syndrome. The anabolic effects of GH and IGF-1 on bone formation are important for the acquisition of bone mass, mainly during childhood and puberty. In TM, GH secretory dysfunction is common and contributes to osteopenia and osteoporosis, along with other endocrinopathies such as hypoparathyroidism and vitamin D deficiency, hypothyroidism and diabetes. Prevention is with no doubt the first step in the management of osteoporosis in TM, with the final goal of preventing bone loss and fractures. The management of patients with TM should start as early as birth in order to minimize the disease complications. Induction of puberty at a proper age with estrogens in girls and testosterone in boys and later treatment of hypogonadism with HRT are vital steps in the prevention of bone disease in TM. Biphosphonates, the well known medication for osteoporosis, have been tried in the treatment of TM-osteoporosis with promising outcomes. Since the origin of bone disease in TM is multifactorial and some of the underlying pathogenic mechanisms are still unclear, further research in this field is needed, which will allow the design of optimal therapeutic measures.

Ref: Ped. Endocrinol. Rev. 2011;8(Suppl 2):300-306

Key words: Thalassaemia, bone disease, osteoporosis, endocrine complications

 

 

β -Thalassemia and Thyroid Failure: IsThere A Role for Thyroid Autoimmunity?

Stefano Mariotti1,MD, Francesca Pigliaru1, MD, Maria Chiara Cocco1, MD, Alessandra Spiga2 MD, Stefania Vaquer2, MD Maria Eliana Lai2, MD

Abstract

Autoimmunity is not believed to be involved in tissue damage of -Thalassemia (-Thal), although nonspecific triggering of autoimmunity by iron overload has been suggested. We recently re-evaluated thyroid function and autoimmunity in 132 -Thal patients born and living in Sardinia Island, where a high prevalence of both β-Thal and autoimmune disease is well documented and in 1002 age and sex-matched euthyroid individuals from the general population. The prevalence of primary hypothyroidism in -Thal patients was 28.7% (38/132), without significant difference between males (M) and females (F). Hypothyroidism was associated with smaller and hypoechoic glands, while no difference in the prevalence of anti-thyroid antibodies (ATA) was found between -Thal patients with or without thyroid failure. Interestingly, the prevalence of ATA in β-Thal women (9.2%) was significantly lower than that found in age-matched euthyroid women (20.0%). Our study confirms that thyroid autoimmunity has no role in the pathogenesis of hypothyroidism in b-Thal. Moreover, the lower ATA prevalence in β-Thal women suggests that iron overload may inhibit rather then trigger thyroid autoimmunity.

Ref: Ped. Endocrinol. Rev. 2011;8(Suppl. 2):307-309

Key words: β-thalassemia, thyroid, hypothyroidism, thyroid autoimmunity, anti-thyroid autoantibodies

 

 

Abnormal Seminal Parameters in Patients with Thalassemia Intermedia and Low Serum Folate Levels

Vincenzo De Sanctis1, MD, Giancarlo Candini2, PhD, Michela Giovannini3, MD, Giuseppe Raiola4, MD, Maurice Katz5, FCP(SA)FRCP

Abstract

Seminal parameters were evaluated in 16 fully mature patients with thalassemia intermedia. Their ages ranged from 19 to 54 years (mean age 27 yrs) and serum ferritin levels varied from 205 to 3400 ng/ml. Eleven patients (68.7 %) had normal seminal parameters, 1 (1.6 %) had oligospermia, 3 (18.7 %) had asthenospermia and 1 (1.6 %) had oligoasthenospermia. A significant positive correlation was observed between the serum ferritin and ALT and serum ferritin and γ-GT (r: 0.636, p: 0.007; r: 0.497, p: 0.048, respectively), ALT and γ-GT (r: 0.749, p: 0.001) and total sperm concentration and serum folate (r: 0.572, p: 0.02). Despite some limitations, our study has useful clinical implications for the treatment of patients with thalassemia intermedia.

Ref: Ped. Endocrinol Rev. 2011;8(Suppl 2):310-313

Key words: Thalassemia intermedia, seminal parameters, folic acid, folate deficiency

 

 

Papillary Thyroid Cancer in Thalassaemia

Maria Rita Govoni1, MD, Monica Sprocati1, MD, Elena Fabbri1, MD, Nicolò Zanforlin1, MD, Vincenzo De Sanctis2, MD

Abstract

Thyroid cancer is the most frequent endocrine neoplasm in the general population. Its incidence is 5-10/100,000 per year, with an annual death rate of 0.2-1.2/100,000 in men and 0.4-2.8/100,000 in women. In thalassaemia patients the frequency of this disease is unknown. In this paper we describe five cases of papillary thyroid cancer in thalassaemia patients followed at the Day Hospital for Thalassaemia and Haemoglobinopathies, in Ferrara, Italy. We consider the possible key role of iron as a carcinogenic agent and we also discuss the practical implications of our clinical observations.

Ref: Ped. Endocrinol. Rev. 2011;8(Suppl 2):314-321

Keywords: Thyroid cancer, thalassaemia, iron overload, risk facto

 

 

Acquired Central Hypothyroidism in A Male Thalassaemic Patient With Severe Iron Overload

Vincenzo De Sanctis MD1, Michela Giovannini MD2

Abstract

Acquired central hypothyroidism (CH) is a rare form of hypothyroidism that results from a variety of conditions affecting the hypothalamus and the pituitary gland. This pathology remains difficult to diagnose in patients with chronic disease. The Authors describe a 21-year-old patient with thalassaemia (TM) who was referred for the evaluation of short stature and hypogonadism, and was found to have CH.

This case report stresses the importance of following thyroid function in TM patients and underlines the criteria for diagnosis and treatment.

Ref: Ped. Endocrinol Rev. 2011;8(Suppl 2):322-323

Key words: Thalassaemia, central hypothyroidism, iron overload

 

 

Adrenal Incidentaloma in Thalassemia: A Case Report and Literature Review

Maria Rita Gamberini1, MD, Napoleone Prandini2, MD, Elisabetta Chiodi3, MD, Carlotta Farneti1, MD, Maria Chiara Garani1, MD

Abstract

In the last 30 years the development and widespread use of modern imaging techniques has caused a 20-time increase in the diagnosis of adrenal incidentaloma (AI). Among AIs myelolipoma (ML) is reported with a frequency up to 10%. In the literature 8 patients with adrenal masses in thalassaemia or chronic haemolytic anaemia have been reported: five cases were shown to have extramedullary haematopoiesis (EH) and 3 ML. We describe here a case of an adult male affected by beta thalassaemia intermedia and large bilateral lipomatous adrenal masses. The patient was referred to our ward at the age of 55 and underwent hormonal testing, MRI, and SPECT/CT scans. Adrenal masses were hormonally inactive, and fat-containing on MRI and CT scans. SPECT/CT examination with 99mTccolloid demonstrated the presence of marrow tissue. ML and EH are the only two tumours with marrow tissue among lipomatous adrenal masses. In our patient a brown nodular mass was resected and histologically classified as ML. In benign adrenal masses, radiological follow-up is indicated; in case of large bilateral masses adrenal function tests are suggested periodically in order to detect possible adrenal hypofunction.

Ref: Ped. Endocrinol. 2011;8(suppl. 2):324-330

Key words: Incidentaloma, Myelolipoma, Thalassaemia

 

 

Diffuse Intracerebral Calcification in a Beta-Thalassaemia Major Patient with Hypoparathyroidism: A Case Report

Mojtaba Mahmoodi MD1, Vincenzo De Sanctis MD2, Mehran Karimi MD

Abstract

Beta-thalassemia major is a complex medical problem found worldwide. Endocrinopathies are some of the most frequent dysfunctions found in these patients. Iron overload in different organs is responsible for multiple endocrine complications particularly in the absence of adequate chelation therapy. One of the most prevalent endocrine complications of thalassemia major is hypoparathyroidism. It can cause cerebral calcifications in the basal ganglia but seldom outside of the extrapyramidal system. There are few studies about intracerebral calcification due to hypoparathyroidism in patients with thalassemia major. We report the case of a 14 year-old girl who came to our Center with the chief complaint of a generalized tonic-clonic seizure. The patient was known to have beta-thalassemia major since she was 9 months old. Computerized tomographic scan of the brain was done which showed diffuse intracranial calcifications in deep white matter, posterior fossa, basal ganglia and both thalami. Laboratory and neuroimaging assessments revealed the diagnosis of hypoparathyroidism. We strongly recommend periodic assessment and tight control of serum calcium level in all patients with betathalassemia major. Prompt treatment with oral calcium supplements and an active form of vitamin D can prevent hypoparathyroidism and its neurologic complications. Comprehensive evaluation and treatment of other endocrinopathies in accordance with hypoparathyroidism is suggested.

Ref: Ped. Endocrinol. Rev. 2011;8(Suppl 2):331-333

Keywords: Beta-thalassemia major, hypoparathyroidism, intracerebral calcification.

 

 

Generalized Tonic-Clonic Seizures in a Thalassemic Patient with Hypoparathyroidism and Brain Calcinosis

Vincenzo De Sanctis1, MD, Michela Giovannini2,MD, Sara Ciccone2, MD, Mehran Karimi3, MD

Abstract

Acquired hypoparathyroidism (HPT) is a not uncommon complication in patients with b-thalassemia major. The insufficient production of parathyroid hormone is mainly due to iron overload in parathyroid glands. We report a 22-year-old female thalassemic patient referred to our Unit for hypogonadism. During the previous two years she had presented with tonic-clonic seizures. After the second episode the patient was treated with phenytoin and valproate. Laboratory investigations were compatible with a diagnosis of HPT. A computed tomography scan of the head showed diffuse cerebral calcifications in the basal ganglia, frontal subcortical white matter, lentiform nucleus and cerebellum. After treatment with oral calcium supplementation and calcitriol she did not experience any further seizures. In addition, we present a brief review of the literature and report the Authors’ recommendations.

Ref: Ped. Endocrinol. Rev. 2011;8(suppl 2):334-336

Key words: hypoparathyroidism, seizures, brain calcinosis, thalassemia

 

 

Case Report: Thalassemia Intermedia Patient with Hypertension Non- Responsive To Combined Medical Treatment

Maria Eliana Lai, MD, Stefania Vacquer, MD, Maria Paola Carta, MD, Claudia Corrias, PhD, Alessandra Spiga, MD

Abstract

Pheochromocytoma is a rare disease in the general population and, to the best of our knowledge, only one case has been reported so far in patients with hemoglobinopathies. We describe the occurrence of pheochromocytoma in a patient with thalassemia intermedia associated with Gilbert’s disease and Crigler- Najjar Type 2 syndrome.

Ref: Ped. Endocrinol Rev. 2011;8(Suppl 2):337-339

Key words: Thalassemia intermedia, paroxysmal hypertension, pheochromocytoma

 

 

Paraplegia in a Thalassaemic Patient with Short Stature

Saveria Campisi1, MD, Antonino Mangiagli2, MD, Vincenzo De Sanctis3,MD, Michela Giovannini4,MD

Abstract

Extramedullary hematopoiesis (EMH) is a normal compensatory reaction that occurs in almost all chronic hemolytic anemia, especially in transfusion independent thalassemia intermedia, and can involve many organs or tissues, including the epidural space leading to spinal cord compression syndrome. We present a case of EMH in a 29 year old woman with thalassemia major, regularly transfused since the time of diagnosis (age 21 months), who presented with sudden muscle weakness, difficulty walking and maintaining the upright position. Magnetic Resonance Imaging (MRI) of the thoracic spine showed spinal cord compression secondary to extramedullary hematopoiesis in the spinal canal, leading to early therapy. The neurosurgical treatment (decompressive laminectomy D3-D6) in our patient brought a significant and rapid recovery. The next two MRI of the spine (after 6 and 18 months) were both negative for recurrence.

Ref: Ped. Endocrinol. Rev. 2011;8(Suppl 2):340-344

Key words: Thalassaemia major, extramedullary haematopoiesis, treatment, surgery

 

 

Absence of Teratogenicity of Deferasirox Treatment during Pregnancy in a Thalassaemic Patient

Salvatore Anastasi, MD1, Roberto Lisi, MD1, Giovanna Abbate, MD1, Vincenzo Caruso, MD1, Michela Giovannini, MD2, Vincenzo De Sanctis, MD

Abstract

A 34–year-old female thalassaemia major patient regularly followed in our Thalassaemia Centre was diagnosed at 16 years of age with primary amenorrhea. The endocrine investigations were compatible with hypogonadotropic hypogonadism. Puberty was induced with oral oestrogens and progesterone, followed by transdermal hormone replacement therapy. She had initiated regular blood transfusions at 8 months of age and iron chelation therapy with desferioxamine at the age of 2 years, and in 2006 she was switched to treatment with the oral iron chelator deferasirox (DFX). In November 2009, the patient reported a temporary interruption of transdermal hormone replacement therapy during the previous July and August, and complained of the absence of menstrual flow since then. We suspected a pregnancy that was confirmed by pelvic ultrasound (presence of a fetus of 20 weeks’ gestational age) and positive plasma b-hCG levels (14000 mIU/ ml). DFX was immediately discontinued and the patient was managed jointly with an obstetrician expert in haemoglobin disorders. In March 2010 she delivered via caesarean section, at 38 weeks of gestation, a male neonate with a weight of 3.300 Kg with no complications or malformations. The main messages from this patient are that: (i) the hypogonadotropic hypogonadism, secondary to iron overload, may be reversible, (ii) transdermal hormone replacement therapy and regular iron chelation therapy may have had a synergistic action on the activation of hypothalamic-pituitary-gonadal axis, (iii) the deferasirox treatment during pregnancy may be harmless for the fetus at the usually recommended therapeutic doses, (iv) periodic patient education is needed in order to fully explain the aim and the effects of sex steroid hormone replacement therapy given transdermally. The Authors discuss the current knowledge on iron chelation therapy during pregnancy. They believe that the safest approach is to make sure that iron levels are really well controlled before pregnancy, to allow for an interruption of chelation.

Ref: Ped Endocrinol. Rev. 2011;8(Suppl 2):345-347

Key words: Thalassaemia, pregnancy, deferasirox, endocrine complications, hormone replacement therapy